The overall aim of the proposed study is to elucidate the immunopathogenesis of IgA nephropathy and allied diseases. All adult and pediatric patients who have IgA as the predominant immunoglobulin in the glomerular mesangium are potential subjects. We plan to: 1) determine if specific antibodies in serum and secretions (blood, tears, saliva and intestinal washings) to milk proteins correlate with the presence of free or Ig-coupled antigen after an acute challenge with milk. IgA and immune complexes (IC) will be characterized by amount, subclasses, titers to specific milk proteins, IgA and IgM rheumatoid factors, and IC within macrophages and bound to polymorphonuclear leukocytes or erythrocytes (RBC). Changes in IC levels, if any, will be correlated with acute changes in the magnitude of urinary protein and RBC excretion; 2) characterize the IgA produced by lymphocytes obtained from bone marrow, duodenal lamina propria, and peripheral blood by immunofluorescent staining, cell culture and after Epstein-Barr virus transformation. In addition, the clonal diversity of these cells for the variable region of heavy chains (VH) will also be determined with a panel of monoclonal antibodies; 3) characterize circulating IgA by IgA2 allotype and VH determinants in blacks who only rarely suffer from these diseases; 4) search for circulating IgA antibodies to structural proteins of the mesangium; 5) determine the density and presence of complement receptor (CR1) on RBC's; 6) characterize the ligand specificity, affinity, and binding requirements for IgA on RBC's; and, 7) study the interaction between complement and IC composed of various mixtures of IgG and IgA, including solublization by the classical and alternative pathway and fixation of C3b. All of these aims are focused on the production and clearance of IgA-containing IC in patients with IgA nephropathy in an effort to elucidate the immunopathogenesis of this common form of glomerulonephritis in man as well as basic mechanisms in IgA metabolism.